We are applying to become a collaborative treatment site for the NIDA-sponsored clinical trial comparing the efficacy of Supportive-Expressive Psychotherapy, Cognitive Behavior Therapy, and/or Drug Counseling in cocaine abuse disorders. In addition to conducting the comparative trial (as finalized by the steering committee), we propose a comprehensive investigation of the reliability, stability, and clinical significance of affective disorder diagnoses in cocaine abusers. This substudy has considerable public health significance: while affective disorders are apparently common in cocaine abusers (lifetime prevalence of up to 50%), the reliability of such diagnoses is questionable, their etiopathogenesis is poorly understood, and their implications for treatment planning remain controversial. Features of our substudy include: collection of life-time history and time-course of affective symptoms in relation to cocaine abuse; re-ratings of videotaped interviews and repeat interviews after 1 and 6 months to determine reliability and temporal stability; use of an alternate diagnostic format (SADS) to establish convergent validity; and construct validation of affective disorders diagnoses using the RDC Family History method. In addition, psychotherapy/counseling nonresponders will enter an 8-week placebo-controlled study of the efficacy of desipramine hydrochloride (DMI), with patients stratified by therapy assignment and presence/absence of affective disorder. We hypothesize that cocaine abusers with comorbid affective disorder will have less extensive drug abuse histories, less personality pathology, greater familial risk of affective disorder, superior response to psychotherapy, and lower rates of cocaine use during follow-up. Further, we hypothesize a disaggregation of affective disorder cases into primary and secondary subtypes (on the basis of the temporal sequence of onset in relation to cocaine abuse). We predict that primary depressives will show: earlier onset of depression, less drug exposure, lower levels of intercurrent life stress, more classical signs of melancholia, lower familial risk of substance abuse and higher risk -of affective disorder, more favorable response to DMI, and greater risk of depressive relapse despite abstinence from cocaine. This substudy will yield a wealth of information about the diagnosis and treatment of depression in cocaine abusers, which promises to result in refinements in classification and improved application of the differential therapeutics of these comorbid conditions. These findings thus are likely to lead to a better match between patients and available treatments of cocaine dependence (i.e., drug counseling, professional psychotherapy, and antidepressant pharmacotherapy).